Novel alpha-cyano esters of isocyanic acid and alpha-cyanoalkylcarbamoyl halides effective as intermediates for herbicidal agents

ABSTRACT

THIS INVENTION RELATES TO NOVEL A-CYANO ESTERS OF ISOCYANIC ACID AND A-CYANOALKYLCARBAMOYL HALIDES. IT ALSO RELATES TO A PROCESS FOR THE MANUFACTURE OF SAID COMPOUNDS AND TO THE USE OF SAID COMPOUNDS IN THE PREPARATION OF EFFECTIVE HERBICIDAL AGENTS.

United States Patent Ofiice 3,803,208 Patented Apr. 9, 1974 NOVEL a-CYANO ESTERS F ISOCYANIC ACID AND u-CYANOALKYLCARBAMOYL HALIDES EFFECTIVE AS INTERMEDIATES FOR HERBI- CIDAL AGENTS Karoly Szabo, Stiegengasse 4/16, A-l060 Vienna, Austria, anglvenkat Rao Ganti, 21 Caton Drive, Dewitt, N.Y. 13 4 No Drawing. Filed May 8, 1972, Ser. No. 251,480

Int. Cl. C07c 121/16, 121/46, 121/66 US. Cl. 260465.4 4 Claims ABSTRACT OF THE DISCLOSURE This invention relates to novel a-cyano esters of isocyanic acid and a-cyanoalkylcarbamoyl halides. It also relates to a process for the manufacture of said compounds and to the use of said compounds in the preparation of effective herbicidal agents.

This invention relates to novel compounds having the formula:

wherein R represents a member selected from the group consisting of NCO and NHCOCl; R is methyl, ethyl, or when taken together with R forms a cycloalkyl group having from 3 to 6 carbon atoms; R represents a member selected from the group consisting of alkyl C -C cycloalkyl C -C or where R is hydrogen, halogen, or loweralkyl C -C n is an integer selected from the group 0, l, and 2 and m is an integer selected from the group 0, 1, 2, and 3.

The invention also relates to a process for the preparation of the above-identified u-cyano ester of isocyanic acid and a-cyanoalkylcarbamoyl halides. These compounds are useful as intermediates in the synthesis of highly effective herbicidal agents.

In accordance with the present invention, compounds of the structure:

R Rt-C-Rr wherein R, R and R are as described above, can be prepared by first reacting the appropriate ketone with an alkali metal cyanide, such as sodium or potassium cyanide, and an ammonium salt, preferably the halide or sulfate, in the presence of ammonium hydroxide. The reaction is generally conducted in aqueous solution or in an aqueous-alcoholic mixture, the alcohol preferably being a lower alkanol of from 1 to 4 carbon atoms. Although the reaction may be carried out at room temperature, it is frequently found desirable to heat the reaction mixture to about 40 C. to 100 C., but preferably 40 C. to 55 C.

This reaction yields the aminonitrile corresponding to the ketone employed. The reaction is graphically illus trated below using KCN as the alkali metal cyanide and ammonium hydroxide as the base.

wherein R is methyl, ethyl, or when taken together with R forms a cyanoalkyl C -C R is alkyl C -C (either straight or branched chain), cycloalkyl C -C or (Ra)m where R is hydrogen, halo or loweralkyl C -C n is 0, 1, or 2 and m is 0,1, 2, or 3.

Where desired the aminonitrile is converted to its hydrohalide salt, preferably its hydrochloride salt, by dissolving the free base in anhydrous ether; for example, diethyl ether, tetrahydrofuran, or ethyl ether, and then admixing with said solution the desired hydrohalide. Generally, it is most convenient to mix the acid with anhydrous ether and add this mixture to the ether solution of aminonitrile. The hydrohalide salt precipitates and can be filtered off.

The aminonitrile, or the hydrohalide salt thereof, is then dissolved or dispersed in an aprotic solvent, such as acetone, ethyl acetate, benzene, toluene, diethyl ether, tetrahydrofuran, or the like. This solution may then be cooled to about 0 C. to 10 C. and treated with phosgene gas or a solution of phosgene in aprotic solvent, as described above, may be prepared and the aminonitrile solution added to it. In both process techniques, however, the reaction is conducted at a low temperature, preferably about 0 C. to 10 C., although lower temperatures may be used. When admixture of the phosgene (with or without a base, such as anhydrous alkali metal carbonate, or an organic tertiary amine) with the aminonitrile has been completed, regardless of the process used, the carbamoyl chloride corresponding to the aminonitrile can be recovered from the solution. This is usually accomplished by filtering the reaction mixture and evaporating the filtrate under reduced pressure. Where the corresponding isocyanate is desired, the reaction mixture is heated to reflux, then cooled and the solvent evaporated. Generally, about 1 to 2 moles of phosgene per mole of aminonitrile is satisfactory for the reaction. Graphically, the reaction may be illustrated as follows:

wherein R and R are as described above. Reflux temperature for the latter reaction is generally between about 40 C. to C., and preferably 40 C. to 60 C.

As previously indicated, the wcyano esters of isocyanic acid and the a-cyanoalkylcarbamoyl halides, which have the formula:

where R is -NCO or NHCOCl, and R and R are as described above, are useful for the preparation of effective herbicidal agents. These compounds may be converted to the active agents by reacting said isocyanate or isocyanic acid ester with a ureido phenol in an aprotic solvent, such as acetone, ethyl acetate, benzene, toluene, diethyl ether, tetrahydrofuran, or the like. The reaction is carried out in the presence of a weak base, such as sodium or potassium carbonate or organic tertiary amine, such as triethylamine. The reaction is usually exothermic and does not require heating. It is advantageous to employ at least a molar equivalent of base when using NHCOC1. Graphically, it may be illustrated as follows:

EXAMPLE 1 2-amino-2,3,3-trimethy1butyronitrile (C OZCfiCCHI KCN NHACI NHrOH O NH: l (CHQMC C CH;

To a two-liter flask is added 66 grams of KCN dissolved in 120 ml. of water, along with a magnetic stirring rod. When almost all of the cyanide is dissolved, 140 ml. of water containing 61 grams of NH Cl is introduced into the flask followed by the addition thereto of 67 ml. of concentrated ammonium hydroxide. A solution of the ketone, i.e., 100 grams of pinacolone in 150 ml. of methanol, is added to the mixture and stirred. The mixture was heated to 45 C. to 55 C. for 18 hours and the solvent evaporated to yield the product, a dark heavy oil.

The hydrochloride salt is then obtained by dissolving the oil in anhydrous diethyl ether and admixing therewith hydrochloric acid, preferably in anhydrous diethyl ether. The mixture is filtered and the solvent removed by evaporation under reduced pressure leaving the hydrochloride salt of the aminonitrile.

EXAMPLE 2 2-amino-2-methylbutyronitrile Methyl ethyl ketone (72 grams) is mixed with 73 grams of ammonium sulfate. To this suspension is then added 200 ml. of solvent ether. The mixture is then stirred at 20 C. to 25 C. (slight cooling). A solution of sodium cyanide (50 grams in 200 ml. of water) is then added dropwise during one hour and the reaction mixture stirred for 7 to 10 hours. The inorganic salts were filtered off and aqueous layer extracted three times with 200 ml. portions of ether. All ether extracts are combined, dried over anhydrous potassium carbonate, and then concentrated by evaporation under vacuum.

The residue is distilled at mm. to give 45 to 50 grams of product with boiling point 68 C.

EXAMPLE 3 Following the procedure of Example 1, but substituting the appropriate ketone for pinacolone, yields the corresponding aminonitriles reported in Table 1 below. The hydrochloride salts of each are likewise prepared as described in Example 1.

Ketone Amlnonltrlle N H Rr-F-Rz KON NH4G1 NHAOH v R;Jl-R

N TABLE I Ketone/amlnonitrlle Metllgylun'--- lIWethyl. 1

o sopro Do..-...--; Phen li Ethyl. Buty Cyclohexyl Cyclopentyl Methyl t-Butyl.

Do. n-Propyl Do. see-Butyl Do. enzyl. D0. Phenethyl EthyL- Benzyl. Methyl. Cyclopropyl. Do. 2-ethylbutyl. Eth 1.. Cyclobutyl. Met yl. p-Ohlorophenyl.

o. 2,3-dichlorophenyl.

. Ohlorophenethy lhexyl.

EXAMPLE 4 l-cyano-l,2-dimethylpropyl isocyanate ON CN CH;(EGH(CH COO-h CH;(BCH(CH;)

NHa-HCI N110 0 Cl ON GH3&-CH(CH|)2 NCO Forty-one grams of 2-amino-2,3-dimethylbutyronitrile hydrochloride is dispersed in 220 ml. of ethyl acetate. The suspension is stirred and phosgene gas bubbled through said suspension. The suspension is gently heated (40 C. to 45 C.) for three hours, then the phosgene and ethyl acetate are removed by heating on a water bath at C. The residue is taken up in dry hexane, filtered and the hexane evaporated to yield 15 grams of product, refractive index 11 1.4260.

GOO]:

0 C. to 5 C.

25.2 grams of Z-amino-2,4-dimethylpentanonitrile was dissolved in ml. of anhydrous ether; '50 ml. of ether saturated with HCl is then added. The precipitated HCl salt is filtered off and dried in a dessicator. The total HCl salt is then used for the conversion to isocyanate using anhydrous reagent grade ethyl acetate as solvent.

The HCl salt is dispersed in 100 ml. of the ethyl acetate and slowly added to a stirred, cold (0 C. to 5 C.) solution of phosgene (80 grams) in ml. of ethyl acetate. Stirring is continued for one hour, then cooling discontinued and the reaction mixture refluxed.

The mixture is cooled and the solvent evaporated under reduced pressure. The residue is extracted with hot hexane and the product recovered by distillation. The product had boiling point 47 C. to 54 C./0.75 mm.; 12;, 1.4460.

EXAMPLE 7 l-cyano-l-methylpropylisocyanate NH: NCO OH:- -CH:CH3 CH;-('JCH2-CH;

N N 2-amino-2-methylbutyronitrile (39.2 grams) is dissolved in 100 ml. of dry ethyl acetate and added dropwise to a solution of 80 grams of phosgene in 150 ml. of ethyl acetate with vigorous stirring during one hour. The temperature should not be allowed to go over 5 C.

After all the aminonitrile is added, the cooling is discontinued, phosgene gas passed in, and the mixture heated to reflux. Almost all the solid goes into solution, resulting in a golden yellow color. The time of passage of phosgene is 2. to 2% hours.

Most of the ethyl acetate is removed by distillation by heating on a water bath, leaving a thick viscous residue, which on distillation yields the product, boiling point 54 C. 56 C. at 12 to 14 mm.; 11 1.4165.

This procedure is followed with appropriate aminonitrile substitutions to yield the esters of isocyanic acid and isocyanates, reported in Table II.

To a suspension of 1,1-dimethyl 3- (m-hydroxyphenyl)- urea (620 mg.) in 5 ml. of dry reagent grade acetone, a drop of triethylamine is added, followed by 420 mg. of l-cyano-l-methylpropylisocyanate all at once. The reac tion is very exothermic and a clear solution results. After standing for 15 minutes, a crystalline mass comes out of solution. The product (1.0 gram) is filtered off and washed with ice-cold acetone to give a melting point of 145 C. to 147 C.

EXAMPLE 9 m-(3-methoxy-3-methylureido) phenyl l-cyano-lmethylpropyl)-carbamate TABLE II COC1z0 C. to 5 C. ethyl acetate halid C0011 0 C. to 5 C. ethyl acetate.

Aminonitrile ON I-CH1 NHa-HCI Same as above- NHrHCl EXAMPLE 8 m-(3,3-dimethylureido)phenyl (l-cyano-l-methylpropyl) carbamate 0H nz-Cyanoalkylcarbamoyl C--G a NHCOCI Cm-C-NH-C 0 Cl NHCOCI Isoeyanate characterization Isoeyanate CN l C H;

at 1.25 mm.

I NCO B.P. 52-54 C.

at 0.5-0.7 mm.-

at 1-2 mm.

7 EXAMPLE m} (3 -methoxy-3 -methylureido) phenyl l-cyano- 1- methylethyl) -carbarnate m- (3-methoxy-3-methylureido) phenyl l-cyanolmethylethyl) -carbamate a CHz-C-NHC 0 G1 I CN CH: EhN l CHI OCH 1 (3 CH1 V, H N

HO 0NCHI(OCH3) 4O 8 ture for a further 30 minutes at 60 C. to 67 C. and the reaction mixture became clear, was filtered and evaporated under reduced pressure to a colorless oil. The infrared spectrum showed very intense absorption at 1740 to 1780 cm.- assignable as the carbamoyl chloride The crude carbamoyl chloride was added to 3-(m-hydroxyphenyl) l-methoxy-l-methyl urea (17.64 grams, 0.09 mole), triethylamine (11 grams, 0.11 mole) in ethyl acetate (50 ml.) at C. A solid precipitated, further trict hylamine (2 grams, 2 moles) was added after the addition and the reaction mixture temperature rose to 33 C., was cooled to 18 C. for minutes and filtered. The filtrate was evaporated almost to dryness, then wateracetone added and a further 2.3 grams (9%), melting point 157 C. to 160 C. was obtained. Total yield 22.4 grams (89%). The solid was stirred with Water and dried to give 20.1 grams (30%), melting point 167 C. to 168 C.

EXAMPLE 12 The herbicidal activity of carbamate compounds prepared from the esters of isocyanic acid and from the isocyanates of the present invention is demonstrated in the following post-emergence tests. In these tests, ten-day old crabgrass, yellow foxtail, wild oats, mustard, bindweed and bush ben plants are sprayed with 35 65% water/ acetone solutions of test compound. Each flat was sprayed with 15 ml. of solution containing mg. of compound. The sprayed plants were then placed on greenhouse benches and cared for in accordane with normal greenhouse procedures. Three weeks after treatment, all plants were examined and rated. The results obtained appear in Table III below.

TABLE III.-POSTEMERGENCY ACTIVITY Percentkill Compound gi s t r 35$ b 2252 o H ON 100 100 100 100 100 100 Dita-(B411.

OCH: NHC-N 0 H OH. Stunted 100 100 100 100 100 oil-Lac:

HFOH:

NC-N-(CH:): 11.",

To a phosgene solution (12 grams, 0.12 mole) in dry EXAMPLE 13 ethyl acetate (180 ml.) cooled to 0 'C. was added anhydrous sodium carbonate (1.5 grams, 0.14 mole), then dropwise with cooling Zunethyl-Z-aminopropionitrile (8.4 grams, 0.1 mole) in ethyl acetate (40 ml.). A white solid was formed during the addition. After one hour the reaction mixture was allowed to attain reaction temperature (20 C.). Then it was gradually warmed to C. taking 30 minutes. Further phosgene was passed through the mix- 75 Postemergence activity of the carbamates prepared from the esters of isocyanic acid and the isocyanates of the present invention is further demonstrated by the following tests. In these tests, compounds are applied to twoweek-old plants in a 35%/65% water/acetone mixture containing sufficient compound to provide the equivalent of 4 pound per acre of active compound. After spraying, the plants are placed on greenhouse benches and cared Percent difference in growth from the check 1 Rating system: rated (Table IV) according to the index given below: 1

5 on the rating scale.

15 Based on visual determination of stand, vigor, chlorosis,

growth malforma'tion, and over-all plant appearance.

RAG--ragweed MU-mustard LAlambsquartcrs TABLE IV.-POSTEMERGENCE ACTIVITY Rating MG COT SB BOY W0 BA FOX RAG MU LA Compound C C C n n J N H O nw O (u) H ON O-(J-Ni 1k 0 CH:

TABLE IV-Continued Rating Compound was com SB SOY wo BA FOX RAG MU LA H on 3, 7, a 1 2 9 a 9 9 (ea-NE OCH:

N-C-N Y 5 9 9 o s 1 9 9 a a 9 a 5 9 7 5 9 9 a a 0 H CN o o s 5 9 0 O--(I.|,--I!I-(!}(CH:)|OH| CHgCHI N-C-N I l 4; \CHI We claim: I 4. The compound according to claim 1: 1.Acompound having the structure: NHCOCI M10001 GHP where R, is halogen or C -C akyl, n is an integer from 0 to 2 and m is an integer from 0 to 3.

2. The compound according to claim 1:

ON OHr--CH-(CHa):

M30001 3. The compound according to claim 1:

UNITED References Cited STATES PATENTS Farrissey et a1. 260-465.4 X

Brotherton et a1. 260465 D X Zenner et al. 260-465 D X Kampe 260-4654 X Sayigh et a1. 260465.4 X Koenig et al. 260-4654 X Sayigh et a1. 260465 D X OTHER REFERENCES singer et 1.; c. A. 61 (1964), p. 9452. Knabe et aL: C. A. 73 (1970), pp. 279-280, section Derwent Belgi (Jan. 8, 1968).

an Petent Report, No. 49/67, p. 3:4-5

JOSEPH P BRUST, Primary Examiner US. Cl. X.R. 

